text: In RCM reactions, two possible geometric isomers, either E- or Z-isomer, may be formed. Stereoselectivity is dependent on the catalyst, ring strain, and starting diene. In smaller rings, Z-isomers predominate as the more stable product reflecting ring-strain minimization. In macrocycles, the E-isomer is often obtained as a result of the thermodynamic bias in RCM reactions as E-isomers are more stable compared to Z-isomers. As a general trend, ruthenium NHC (N-heterocyclic carbene) catalysts favor E selectivity to form the trans isomer. This in part due to the steric clash between the substituents, which  adopt a trans configuration as the most stable conformation in the metallacyclobutane intermediate, to form the E-isomer. The synthesis of stereopure Z- isomers were previously achieved via ring-closing alkyne metathesis. However, in 2013 Grubbs reported the use of a chelating ruthenium catalyst to afford Z macrocycles in high selectivity. The selectivity is attributed to the increased steric clash between the catalyst ligands and the metallacyclobutane intermediate that is formed. The increased steric interactions in the transition state lead to the Z olefin rather than the E olefin, because the transition state required to form the E- isomer is highly disfavored.